We have replicated the results of a preliminary outpatient study showing that treatment with alpha-tocopherol (vitamin E) decreases symptoms of tardive dyskinesia (TD). This supports the free radical hypothesis of TD. We are planning several additional studies to further explore the neurobiology of TD. These include trials of medications, neuropsychological tests, neuroradiological examinations, and evaluations of eye tracking. We are studying the following three hypotheses: (1) free-radical scavengers reduce the severity of and prevent the development of TD; (2) TD is associated with neuronal cell loss in the striatum; and (3) cognitive impairment is associated with TD in older but not younger patients relative to patients without TD.